میریستین به طور انتخابی سبب القاء آپوپتوز در هپاتوسیت های سرطانی به وسیله هدف قرار دادن میتوکندری های آنها می شود.

صیدی, عنایت اله and راسخ, حمید رضا and سلیمی, احمد and محسنی فر, ژاله and پوراحمد, جلال (1395) میریستین به طور انتخابی سبب القاء آپوپتوز در هپاتوسیت های سرطانی به وسیله هدف قرار دادن میتوکندری های آنها می شود. Basic and Clinical Pharmacology and Toxicology ــ 119 (3). pp. 249-258. شاپا 7835-1742

[img] Text
محدود به Repository staff only


Official URL: https://onlinelibrary.wiley.com/doi/10.1111/bcpt.1...


Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria

English Abstract

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. In patients for whom HCC could not be detected early, current treatments show poor tolerance and low efficacy. So, alternative therapies with good efficacy are urgently needed. The aim of this research was to evaluate the selective apoptotic effects of myricetin (MYR), a flavonoid compound, on hepatocytes and mitochondria obtained from the liver of HCC rats. In this study, HCC induced by diethyl nitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. To confirm the HCC induction, serum levels of alpha-fetoprotein (AFP), AST, AST and ALP and histopathological changes in the liver tissue were evaluated. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effects of MYR were isolated, and mitochondrial and cellular parameters related to apoptosis signaling were then determined. Our results showed that MYR was able to induce cytotoxicity only in hepatocytes from the HCC but not from the untreated control group. Besides, MYR (12.5, 25 and 50 µM) induced a considerable increase in reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane permeabilization (MMP) and cytochrome c release only in cancerous but not in untreated normal hepatocyte mitochondria. MYR selectively increased caspase-3 activation and apoptotic phenotypes in HCC, but not untreated normal hepatocytes. Finally, our finding underlines MYR as a promising therapeutic candidate against HCC and recommends the compound for further studies.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :عنایت اله صیدی
نویسنده :حمید رضا راسخ
نویسنده :احمد سلیمی
نویسنده :ژاله محسنی فر
نویسنده مسئول :جلال پوراحمد
Additional Information:IF: 3.176 Indexed in: ISI, PubMed/Medline, Scopus
کلیدواژه ها (انگلیسی):Hepatocellular carcinoma (HCC), Myricetin, Mitochondria
Subjects:QV pharmacology > QV 600 Toxicology
QV pharmacology
Divisions:School of Pharmacy > Department of Toxicology
ID Code:7575
Deposited By: Dr Ahmad Salimi
Deposited On:03 Mar 1395 10:17
Last Modified:25 Jan 1401 09:06

Repository Staff Only: item control page

Document Downloads

More statistics for this item...